COVID-19 exacerbates unequal food access.
Inequality to food access has always been a serious problem, yet it became even more critical during the COVID-19 pandemic, which exacerbated social inequality and reshaped essential travel. This study provides a holistic view of spatio-temporal changes in food access based on observed travel data for all grocery shopping trips in Columbus, Ohio, during and after the state-wide stay-at-home period. We estimated the decline and recovery patterns of store visits during the pandemic to identify the key socio-economic and built environment determinants of food shopping patterns. The results show a disparity: during the lockdown, store visits to dollar stores declined the least, while visits to big-box stores declined the most and recovered the fastest. Visits to stores in low-income areas experienced smaller changes even during the lockdown period. A higher percentage of low-income customers was associated with lower store visits during the lockdown period. Furthermore, stores with a higher percentage of white customers declined the least and recovered faster during the reopening phase. Our study improves the understanding of the impact of the COVID-19 crisis on food access disparities and business performance. It highlights the role of COVID-19 and similar disruptions on exposing underlying social problems in the US.


Exposure to wild-type AAV drives distinct capsid immunity profiles in humans.
Recombinant adeno-associated virus (AAV) vectors have been broadly adopted as a gene delivery tool in clinical trials, owing to their high efficiency of transduction of several host tissues and their low immunogenicity. However, a considerable proportion of the population is naturally exposed to the WT virus from which AAV vectors are derived, which leads to the acquisition of immunological memory that can directly determine the outcome of gene transfer. Here, we show that prior exposure to AAV drives distinct capsid immunity profiles in healthy subjects. In peripheral blood mononuclear cells (PBMCs) isolated from AAV-seropositive donors, recombinant AAV triggered TNF-α secretion in memory CD8+ T cells, B cell differentiation into antibody-secreting cells, and anti-capsid antibody production. Conversely, PBMCs isolated from AAV-seronegative individuals appeared to carry a population of NK cells reactive to AAV. Further, we demonstrated that the AAV capsid activates IL-1β and IL-6 cytokine secretion in monocyte-related dendritic cells (moDCs). IL-1β and IL-6 blockade inhibited the anti-capsid humoral response in vitro and in vivo. These results provide insights into immune responses to AAV in humans, define a possible role for moDCs and NK cells in capsid immunity, and open new avenues for the modulation of vector immunogenicity.


Snapshot of the eukaryotic gene expression in muskoxen rumen--a metatranscriptomic approach.
Herbivores rely on digestive tract lignocellulolytic microorganisms, including bacteria, fungi and protozoa, to derive energy and carbon from plant cell wall polysaccharides. Culture independent metagenomic studies have been used to reveal the genetic content of the bacterial species within gut microbiomes. However, the nature of the genes encoded by eukaryotic protozoa and fungi within these environments has not been explored using metagenomic or metatranscriptomic approaches. In this study, a metatranscriptomic approach was used to investigate the functional diversity of the eukaryotic microorganisms within the rumen of muskoxen (Ovibos moschatus), with a focus on plant cell wall degrading enzymes. Polyadenylated RNA (mRNA) was sequenced on the Illumina Genome Analyzer II system and 2.8 gigabases of sequences were obtained and 59129 contigs assembled. Plant cell wall degrading enzyme modules including glycoside hydrolases, carbohydrate esterases and polysaccharide lyases were identified from over 2500 contigs. These included a number of glycoside hydrolase family 6 (GH6), GH48 and swollenin modules, which have rarely been described in previous gut metagenomic studies. The muskoxen rumen metatranscriptome demonstrates a much higher percentage of cellulase enzyme discovery and an 8.7x higher rate of total carbohydrate active enzyme discovery per gigabase of sequence than previous rumen metagenomes. This study provides a snapshot of eukaryotic gene expression in the muskoxen rumen, and identifies a number of candidate genes coding for potentially valuable lignocellulolytic enzymes.


Cost-efficient design of occupational exposure assessment strategies--a review.
When designing a strategy for collecting occupational exposure data, both economic and statistical performance criteria should be considered. However, very few studies have addressed the trade-off between the cost of obtaining data and the precision/accuracy of the exposure estimate as a research issue. To highlight the need of providing cost-efficient designs for assessing exposure variables in occupational research, the present review explains and critically evaluates the concepts and analytical tools used in available cost efficiency studies. Nine studies were identified through a systematic search using two algorithms in the databases PubMed and ScienceDirect. Two main approaches could be identified in these studies: 'comparisons' of the cost efficiency associated with different measurement designs and 'optimizations' of resource allocation on the basis of functions describing cost and statistical efficiency. In either case, the reviewed studies use simplified analytical tools and insufficient economic analyses. More research is needed to understand whether these drawbacks jeopardize the guidance on cost-efficient exposure assessment provided by the studies, as well as to support theoretical results by empirical data from occupational life.


Cardiac pacing in the 1980s: treatment and techniques in transition.
The pacemaker of the 1980s is designed to maintain atrioventricular synchrony through dual-chamber pacing. This pacemaker is multiprogrammable and capable of telemetric transmission of biologic, electronic and electrophysiologic data. Several developments have made this therapeutic modality possible: 1) the cumulative survival rate of many lithium-battery pacemakers exceeds 95% at 5 years; 2) lead and connector problems are rare; 3) atrial and ventricular electrode malfunctions occur in less than 2% of implants; and 4) new introducer techniques have simplified implantation (mortality and major morbidity rates are 0.5 and 0.4%, respectively). With multiprogrammability, pacemaker function can be optimized for the patient's needs, and about 20% of reoperations can be avoided. Ninety-six dual-chamber (DDD) pacemakers, 55 of which have been followed up for more than 3 months, have provided trouble-free performance and have yielded salutary clinical results, particularly when implanted to replace previous ventricular inhibited units. Problems with these pacemakers have included unusual pacing electrocardiograms, pacemaker eccentricities, programmer maintenance, pacing and follow-up complexities and costs. In the 1980s, effort will be required to find a balance between rapidly evolving technology and the clinical need for complex pacing systems. From 1978 to 1981, the rate of pacemaker implantation grew from 309 to 513 implants per million population per year, and there are now approximately 500,000 patients with implanted pacemakers living in the United States. Indications for pacing are ill-defined, because in many cases the assessment of clinical response to pacing is largely subjective, lacking satisfactory quantitative indexes. This decade will be a time of reappraisal of the extent of clinical applicability of new techniques, particularly the multiprogrammable dual-chamber system which, after 3 years of clinical trial, shows promise of being the predominant pacemaker of the immediate future.


Effect of training cessation on muscular performance: a meta-analysis.
The purpose of this study was to assess the effect of resistance training cessation on strength performance through a meta-analysis. Seven databases were searched from which 103 of 284 potential studies met inclusion criteria. Training status, sex, age, and the duration of training cessation were used as moderators. Standardized mean difference (SMD) in muscular performance was calculated and weighted by the inverse of variance to calculate an overall effect and its 95% confidence interval (CI). Results indicated a detrimental effect of resistance training cessation on all components of muscular performance: [submaximal strength; SMD (95% CI) = -0.62 (-0.80 to -0.45), P < 0.01], [maximal force; SMD (95% CI) = -0.46 (-0.54 to -0.37), P < 0.01], [maximal power; SMD (95% CI) = -0.20 (-0.28 to -0.13), P < 0.01]. A dose-response relationship between the amplitude of SMD and the duration of training cessation was identified. The effect of resistance training cessation was found to be larger in older people (> 65 years old). The effect was also larger in inactive people for maximal force and maximal power when compared with recreational athletes. Resistance training cessation decreases all components of muscular strength. The magnitude of the effect differs according to training status, age or the duration of training cessation.


Abuse of Older Men in Seven European Countries: A Multilevel Approach in the Framework of an Ecological Model.
Several studies on elder abuse indicate that a large number of victims are women, but others report that men in later life are also significantly abused, especially when they show symptoms of disability and poor health, and require help for their daily activities as a result. This study focused on the prevalence of different types of abuse experienced by men and on a comparison of male victims and non-victims concerning demographic/socio-economic characteristics, lifestyle/health variables, social support and quality of life. Additionally, the study identified factors associated with different types of abuse experienced by men and characteristics associated with the victims. The cross-sectional data concerning abuse in the past 12 months were collected by means of interviews and self-response during January-July 2009, from a sample of 4,467 not demented individuals aged between 60-84 years living in seven European countries (Germany, Greece, Italy, Lithuania, Portugal, Spain and Sweden). We used a multilevel approach, within the framework of an Ecological Model, to explore the phenomenon of abuse against males as the complex result of factors from multiple levels: individual, relational, community and societal. Multivariate analyses showed that older men educated to higher levels, blue-collar workers and men living in a rented accommodation were more often victims than those educated to lower levels, low-rank white-collar workers and home owners, respectively. In addition, high scores for factors such as somatic and anxiety symptoms seemed linked with an increased probability of being abused. Conversely, factors such as increased age, worries about daily expenses (financial strain) and greater social support seemed linked with a decreased probability of being abused. Male elder abuse is under-recognized, under-detected and under-reported, mainly due to the vulnerability of older men and to social/cultural norms supporting traditional male characteristics of stoicism and strength. Further specific research on the topic is necessary in the light of the present findings. Such research should focus, in particular, on societal/community aspects, as well as individual and family ones, as allowed by the framework of the Ecological Model, which in turn could represent a useful method also for developing prevention strategies for elder abuse.


[Follow-up of elderly patients after emergency hospitalization for severe drug reactions].
Forty-one observations concerning persons aged over sixty-five hospitalized for adverse drug reactions in the Emergency Service of Clermont-Ferrand University Hospital were collected and analysed by the Adverse Drug Reaction Monitoring Centre. The symptoms were predominantly haemorrhage, particularly digestive, connected with the use of oral anticoagulants, salicylates and anti-inflammatories. The follow-up of the thirty-one most severe cases (hospitalization over 48 h and/or initial resuscitation) was undertaken in hospital and other care centres. In seventeen cases, complications occurred linked to the hospitalization (especially infections and neuropsychic complications) or to the adverse reaction itself through the measures taken to correct it (particularly cardiovascular complications). The hospitalization revealed hitherto undetected conditions in twelve patients, thereby allowing the prognosis to be improved. This positive side hardly outweighs the detrimental effects of adverse drug reactions in elderly subjects (six deaths and four irreversible incapacitations). Thus vital and social prognosis of elderly appears greatly damaged by adverse drug reactions.


Integrated GlycoProteome Analyzer (I-GPA) for Automated Identification and Quantitation of Site-Specific N-Glycosylation.
Human glycoproteins exhibit enormous heterogeneity at each N-glycosite, but few studies have attempted to globally characterize the site-specific structural features. We have developed Integrated GlycoProteome Analyzer (I-GPA) including mapping system for complex N-glycoproteomes, which combines methods for tandem mass spectrometry with a database search and algorithmic suite. Using an N-glycopeptide database that we constructed, we created novel scoring algorithms with decoy glycopeptides, where 95 N-glycopeptides from standard α1-acid glycoprotein were identified with 0% false positives, giving the same results as manual validation. Additionally automated label-free quantitation method was first developed that utilizes the combined intensity of top three isotope peaks at three highest MS spectral points. The efficiency of I-GPA was demonstrated by automatically identifying 619 site-specific N-glycopeptides with FDR ≤ 1%, and simultaneously quantifying 598 N-glycopeptides, from human plasma samples that are known to contain highly glycosylated proteins. Thus, I-GPA platform could make a major breakthrough in high-throughput mapping of complex N-glycoproteomes, which can be applied to biomarker discovery and ongoing global human proteome project.


Two functional domains conserved in major and alternate bacterial sigma factors.
Sequences of the sigma factors of Escherichia coli and Bacillus subtilis were aligned with the sequences of two sigma-like proteins, HtpR, involved in the expression of heat-shock genes in E. coli, and SpoIIG, necessary for endospore formation in B. subtilis. An internal region is highly conserved in the four proteins and is proposed to be involved in binding of sigma factors to core RNA polymerase. The carboxy-terminal part of the four proteins presents the characteristic structure found in several prokaryotic DNA-binding proteins and is proposed to be involved in promoter recognition.


Enzymatic transition state poise and transition state analogues.
The development of kinetic isotope effect methods for enzymatic reactions has resulted in the systematic determination of enzymatic transition state structure for several distinct chemical reaction mechanisms. Although it is early in the experimental development of the method, examples of concerted nucleophilic displacements (A(N)D(N) or S(N)2), aromatic nucleophilic displacements (A(N)D(N) or S(N)Ar), and both concerted and stepwise dissociative nucleophilic displacements (D(N)A(N) and D(N)A(N); S(N)1 reactions) have been exemplified. The transition state for each reaction exhibits a characteristic extent of bond-breaking and bond-making, defined here as transition state poise. Thus, concerted nucleophilic displacements (S(N)2 or D(N)A(N)) exhibit various extents of residual bond order to the leaving group and to the attacking nucleophile at the transition state. Aromatic nucleophilic displacements reach their rate-limiting transition states before or after formation of the tetrahedral intermediate. Several concerted, symmetric nucleophilic displacements at carbon have been described. Enzymatic transition state poise is summarized in a single diagram of bond orders using the terminology of Jencks. The analysis reveals enzymatic contributions to transition state poise, provides precedent for assignment of reaction types, and summarizes the current status of the experimental characterization of enzymatic transition states. Binding strengths of transition state analogues are readily correlated with transition state poise.


Novel Sources of Witchweed (Striga) Resistance from Wild Sorghum Accessions.
Sorghum is a major food staple in sub-Saharan Africa (SSA), but its production is constrained by the parasitic plant Striga that attaches to the roots of many cereals crops and causes severe stunting and loss of yield. Away from cultivated farmland, wild sorghum accessions grow as weedy plants and have shown remarkable immunity to Striga. We sought to determine the extent of the resistance to Striga in wild sorghum plants. Our screening strategy involved controlled laboratory assays of rhizotrons, where we artificially infected sorghum with Striga, as well as field experiments at three sites, where we grew sorghum with a natural Striga infestation. We tested the resistance response of seven accessions of wild sorghum of the aethiopicum, drummondii, and arundinaceum races against N13, which is a cultivated Striga resistant landrace. The susceptible control was farmer-preferred variety, Ochuti. From the laboratory experiments, we found three wild sorghum accessions (WSA-1, WSE-1, and WSA-2) that had significantly higher resistance than N13. These accessions had the lowest Striga biomass and the fewest and smallest Striga attached to them. Further microscopic and histological analysis of attached Striga haustorium showed that wild sorghum accessions hindered the ingression of Striga haustorium into the host endodermis. In one of the resistant accessions (WSE-1), host and parasite interaction led to the accumulation of large amounts of secondary metabolites that formed a dark coloration at the interphase. Field experiments confirmed the laboratory screening experiments in that these same accessions were found to have resistance against Striga. In the field, wild sorghum had low Area under the Striga Number Progressive curve (AUSNPC), which measures emergence of Striga from a host over time. We concluded that wild sorghum accessions are an important reservoir for Striga resistance that could be used to expand the genetic basis of cultivated sorghum for resistance to the parasite.


Effect of hyperlipidemia on ketoconazole-midazolam drug-drug interaction in rat.
Hyperlipidemia (HL) was previously shown to lower liver uptake of the more potent (-) enantiomer of ketoconazole (KTZ) in rat. The current study examined the possible modifying influence of experimental HL on a KTZ pharmacokinetic interaction with midazolam (MDZ). Normolipidemic and hyperlipidemic rats were administered a single intravenous dose of MDZ (5 mg/kg) with or without a single oral dose of racemic KTZ (40 mg/kg). Serial blood samples were collected over 8 h following MDZ injections via jugular vein cannulas. Plasma was jointly assayed for MDZ and KTZ concentrations using a validated assay. MDZ mean clearance (CL) was unchanged by KTZ coadministration. HL caused a significantly 61% lower MDZ-unbound fraction and decreases in volume of distribution (VD) but by itself had no effect on MDZ CL. This suggested that MDZ could bind to lipoproteins. With KTZ coadministered to hyperlipidemic rats, there were significant decreases in MDZ CL and VD. HL caused a decrease in unbound plasma fraction of oral KTZ but no significant difference in its pharmacokinetics. HL caused a more pronounced KTZ-associated inhibition of MDZ CL. This may be related to the decrease of MDZ's unbound fraction and perhaps to attenuation of CYP3A by HL in the rat.


Randomized controlled pilot study of mindfulness-based stress reduction for persistently fatigued cancer survivors.
Cancer-related fatigue (CRF) is one of the most common, persistent, and disabling symptoms associated with cancer and its treatment. Evidence-based treatments that are acceptable to patients are critically needed. This study examined the efficacy of mindfulness-based stress reduction (MBSR) for CRF and related symptoms. A sample of 35 cancer survivors with clinically significant CRF was randomly assigned to a 7-week MBSR-based intervention or wait-list control group. The intervention group received training in mindfulness meditation, yoga, and self-regulatory responses to stress. Fatigue interference (primary outcome) and a variety of secondary outcomes (e.g., fatigue severity, vitality, disability, depression, anxiety, and sleep disturbance) were assessed at baseline, post-intervention, and 1-month follow-up. Bonferroni correction was employed to account for multiple comparisons. Controls received the intervention after the 1-month follow-up. Participants in both groups were followed for 6 months after completing their respective MBSR courses to assess maintenance of effects. Compared to controls, the MBSR group reported large post-intervention reductions as assessed by effect sizes (d) in the primary outcome, fatigue interference (d = -1.43, p < 0.001), along with fatigue severity (d = -1.55, p < 0.001), vitality (d = 1.29, p < 0.001), depression (d = -1.30, p < 0.001), and sleep disturbance (d = -0.74, p = 0.001). Results were maintained or strengthened at 1-month follow-up, the point at which significant improvements in disability (d = -1.22, p < 0.002) and anxiety (d = -0.98, p = 0.002) occurred. Improvements in all outcomes were maintained 6 months after completing the course. MBSR adherence was high, with 90% attendance across groups and high rates of participant-reported home practice of mindfulness. Mindfulness-based stress reduction is a promising treatment for CRF and associated symptoms.


Evaluation of a single-dose, extended-release epidural morphine formulation for pain control after lumbar spine surgery.
DepoDur, an extended-release epidural morphine, has been used effectively for postoperative pain control following many orthopaedic and general surgery procedures and has provided prolonged analgesia when compared with Duramorph. The goal of this article was to compare the safety and analgesic efficacy of DepoDur versus Duramorph after lumbar spine surgery. A prospective, randomized, double-blind clinical study was completed at a single extended-stay ambulatory surgery center. All patients over 18 undergoing posterior lumbar spine fusions were considered for the study. Sixty patients were randomly assigned to a control or treatment group. The control group received DepoDur before surgery, while the treatment group received Duramorph. Although results show no significant differences between the two groups in postoperative visual analog pain scale scores, use of pain medication, and adverse events, subjects receiving DepoDur were less likely to receive Naloxone and oxygen supplementation, experience nausea or fever, and were more likely to experience hypotension. DepoDur proved to be safe and effective, offering similar prolonged analgesic activity when compared with Duramorph.


Monitor-Watcher Use, Nurses' Knowledge of Electrocardiographic Monitoring, and Arrhythmia Detection.
Electrocardiographic telemetry monitors are ubiquitous in hospitals. Dedicated monitor watchers, either on the unit or in a centralized location, are often responsible for observing telemetry monitors and responding to their alarms. The impact of use of monitor watchers is not known. To evaluate the association of monitor-watcher use with (1) nurses' knowledge of electrocardiographic (ECG) monitoring and (2) accuracy of arrhythmia detection. Baseline data from 37 non-intensive care unit cardiac patient care areas in 17 hospitals in the Practical Use of the Latest Standards for Electrocardiography trial were analyzed. Nurses' knowledge (n = 1136 nurses) was measured using a validated, 20-item online test. Accuracy of arrhythmia detection (n = 1189 patients) was assessed for 5 consecutive days by comparing arrhythmias stored in the monitor with nurses' documentation. Multiple regression was used to evaluate the association of use of monitor watchers with scores on the ECG-monitoring knowledge test. The association of monitor-watcher use with accuracy of arrhythmia detection was examined by χ2 analysis. Of the 37 units, 13 (35%) had monitor watchers. Use of monitor watchers was not independently associated with ECG-monitoring knowledge (P = .08). The presence of monitor watchers also was not significantly associated with the accuracy of arrhythmia detection (P = .94). Although the use of monitor watchers was not associated with diminished nurses' knowledge of ECG monitoring, it also was not associated with more accurate arrhythmia detection. If implementing a monitor-watcher program, critical safety points, such as ensuring closed-loop communication, must be considered.


Reduction of a large fish tissue analyte database: identifying and assessing data specific to a remediation site for risk assessment application.
The Lower Passaic River (LPR) is one of the most heavily industrialized waterways in the US with both historical and continuing discharges of chemicals from point and non-point sources. Significant efforts have been initiated on behalf of public, private, and regulatory entities to restore this degraded urban river. Considerable attention has been devoted to characterizing environmental media with respect to human and ecological risk. As part of these efforts, a wealth of environmental data have been collected and analyzed for a variety of metals, pesticides, organic compounds, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins/furans (PCDD/Fs), and dioxin-like compounds. The objectives of the study described in this paper were two-fold: (1) to generate LPR-specific data for use in human health risk assessment by characterizing concentrations of contaminants in LPR fish tissue samples based on publicly available data using a methodical and transparent approach, and (2) using the resulting data, to calculate the contaminant concentrations in a "Representative Fish," which is a representation of proportional fish tissue concentrations calculated based upon consumption patterns of LPR anglers. The data reduction, processing, and analyses described provide a representative dataset for the conduct of a human health assessment associated with fish consumption from the LPR.


Antibodies to squalene in Gulf War syndrome.
Gulf War Syndrome (GWS) is a multisystemic illness afflicting many Gulf War-era veterans. The molecular pathological basis for GWS has not been established. We sought to determine whether the presence of antibodies to squalene correlates with the presence of signs and symptoms of GWS. Participants in this blinded cohort study were individuals immunized for service in Desert Shield/Desert Storm during 1990-1991. They included 144 Gulf War-era veterans or military employees (58 in the blinded study), 48 blood donors, 40 systemic lupus erythematosus patients, 34 silicone breast implant recipients, and 30 chronic fatigue syndrome patients. Serum antibodies to squalene were measured. In our small cohort, the substantial majority (95%) of overtly ill deployed GWS patients had antibodies to squalene. All (100%) GWS patients immunized for service in Desert Shield/Desert Storm who did not deploy, but had the same signs and symptoms as those who did deploy, had antibodies to squalene. In contrast, none (0%) of the deployed Persian Gulf veterans not showing signs and symptoms of GWS have antibodies to squalene. Neither patients with idiopathic autoimmune disease nor healthy controls had detectable serum antibodies to squalene. The majority of symptomatic GWS patients had serum antibodies to squalene.


Quantification of flagellar motor stator dynamics through in vivo proton-motive force control.
The bacterial flagellar motor, one of the few rotary motors in nature, produces torque to drive the flagellar filament by ion translocation through membrane-bound stator complexes. We used the light-driven proton pump proteorhodopsin (pR) to control the proton-motive force (PMF) in vivo by illumination. pR excitation was shown to be sufficient to replace native PMF generation, and when excited in cells with intact native PMF generation systems increased motor speed beyond the physiological norm. We characterized the effects of rapid in vivo PMF changes on the flagellar motor. Transient PMF disruption events from loss of illumination caused motors to stop, with rapid recovery of their previous rotation rate after return of illumination. However, extended periods of PMF loss led to stepwise increases in rotation rate upon PMF return as stators returned to the motor. The rate constant for stator binding to a putative single binding site on the motor was calculated to be 0.06 s(-1). Using GFP-tagged MotB stator proteins, we found that transient PMF disruption leads to reversible stator diffusion away from the flagellar motor, showing that PMF presence is necessary for continued motor integrity, and calculated a stator dissociation rate of 0.038 s(-1).


Identification and Analysis of lncRNAs by Whole-Transcriptome Sequencing in Porcine Preadipocytes Induced by BMP2.
Bone morphogenetic protein 2 (BMP2) can mediate the signaling of R-Smads and regulate different biological functions, including adipocyte differentiation. Long noncoding RNAs (lncRNAs) can be involved in many important biological processes, including fat metabolism, as miRNA sponges. This study aimed to investigate the molecular mechanism of fat deposition and to provide useful information for the prevention and treatment of lipid-related diseases. lncRNA sequencing was performed to compare and analyze, for the first time, the expression of lncRNAs in BMP2-induced and non-BMP2-induced preadipocytes from Junmu1 pigs. In addition, functional annotation and enrichment analysis of differentially expressed lncRNA target genes were carried out. lncRNAs and mRNAs were compared and analyzed. lncRNAs were identified that may regulate adipogenesis and lipid metabolism. The results give a theoretical basis for further studies on fat deposition mechanisms and provide potential therapeutic targets for metabolic diseases.


A rare case of spondyloarthropathy: Iatrogenic hypoparathyroidism.
Hypoparathyroidism is an endocrinopathy that can develop idiopathically, as well as due to reasons associated with genetics, autoimmunity, surgery and radiotherapy. It usually presents with neuromuscular signs and symptoms, including enthesopathy caused by calcification of the ligament and enthesis sites, soft tissue calcification, hypertension, cataract and extrapyramidal findings due to basal ganglia calcification. Hypoparathyroidism-associated spondyloarthropathy (SpA) is a rarely seen clinical entity. Hypoparathyroidism-associated SpA differs from other inflammatory SpAs in that the results for human leukocyte antigen B27 and inflammatory markers are negative and bone density is normal. The symptoms are relieved by calcium and vitamin D, rather than anti-inflammatory drugs. Due to this difference in treatment modalities, the diagnosis of this type of SpA is important. This article presents the case report of a 52-year-old female patient with iatrogenic hypoparathyroidism accompanied by asymptomatic hypocalcemia and SpA clinic.


Mus81 is essential for sister chromatid recombination at broken replication forks.
Recombination is essential for the recovery of stalled/collapsed replication forks and therefore for the maintenance of genomic stability. The situation becomes critical when the replication fork collides with an unrepaired single-strand break and converts it into a one-ended double-strand break. We show in fission yeast that a unique broken replication fork requires the homologous recombination (HR) enzymes for cell viability. Two structure-specific heterodimeric endonucleases participate in two different resolution pathways. Mus81/Eme1 is essential when the sister chromatid is used for repair; conversely, Swi9/Swi10 is essential when an ectopic sequence is used for repair. Consequently, the utilization of these two HR modes of resolution mainly relies on the ratio of unique and repeated sequences present in various eukaryotic genomes. We also provide molecular evidence for sister recombination intermediates. These findings demonstrate that Mus81/Eme1 is the dedicated endonuclease that resolves sister chromatid recombination intermediates during the repair of broken replication forks.


Cell-specific effects of Dyt1 knock-out on sensory processing, network-level connectivity, and motor deficits.
DYT1 dystonia is a debilitating movement disorder characterized by repetitive, unintentional movements and postures. The disorder has been linked to mutation of the TOR1A/DYT1 gene encoding torsinA. Convergent evidence from studies in humans and animal models suggest that striatal medium spiny neurons and cholinergic neurons are important in DYT1 dystonia. What is not known is how torsinA dysfunction in these specific cell types contributes to the pathophysiology of DYT1 dystonia. In this study we sought to determine whether torsinA dysfunction in cholinergic neurons alone is sufficient to generate the sensorimotor dysfunction and brain changes associated with dystonia, or if torsinA dysfunction in a broader subset of cell types is needed. We generated two genetically modified mouse models, one with selective Dyt1 knock-out from dopamine-2 receptor expressing neurons (D2KO) and one where only cholinergic neurons are impacted (Ch2KO). We assessed motor deficits and performed in vivo 11.1 T functional MRI to assess sensory-evoked brain activation and connectivity, along with diffusion MRI to assess brain microstructure. We found that D2KO mice showed greater impairment than Ch2KO mice, including reduced sensory-evoked brain activity in key regions of the sensorimotor network, and altered functional connectivity of the striatum that correlated with motor deficits. These findings suggest that (1) the added impact of torsinA dysfunction in medium spiny and dopaminergic neurons of the basal ganglia generate more profound deficits than the dysfunction of cholinergic neurons alone, and (2) that sensory network impairments are linked to motor deficits in DYT1 dystonia.


Validation of a new symptom outcome for knee osteoarthritis: the Ambulation Adjusted Score for Knee pain.
Validation of a symptom measure for early knee OA may help identify new treatments and modifiable risk factors. Symptom measures that consider pain in the context of activity level may provide better discrimination than pain alone. Therefore, we aimed to compare sensitivity to change for radiographic progression between Ambulation Adjusted Score for Knee pain (AASK), which accounts for self-reported ambulation, and Western Ontario McMaster Osteoarthritis (WOMAC) knee pain score. Participants were assessed annually up to 48 months using WOMAC, Physical Activity Scale for the Elderly (PASE) ambulation, and knee radiographs. AASK was defined as ((WOMAC pain) + 1)/((average daily hours of walking) + 1). Radiographs were scored for Kellgren-Lawrence (KL) grade. Linear regression, stratified by OA status, evaluated relationships between changes in AASK and WOMAC pain and KL grade over time. For 4191 people (8030 knees), the mean age was 61.2 (+ 9.2) years old and BMI was 28.6 (+ 4.8) kg/m2; 58% female. Over 40% of knees had WOMAC pain scores of 0; by design, no knees had AASK scores of 0. Annual changes in AASK were more sensitive to changes in KL than changes in WOMAC in those without baseline OA (0.20 and 0.16 change per unit KL change, p = 0.005 and 0.070 respectively), but performed similarly in knees with OA. AASK is simple to assess using existing validated questionnaires. AASK performs well in individuals with and without OA and should be considered in clinical trials and observational studies of early knee OA.


Neurotrophic gene polymorphisms and response to psychological therapy.
Therapygenetics, the study of genetic determinants of response to psychological therapies, is in its infancy. Here, we investigate whether single-nucleotide polymorphisms in nerve growth factor (NGF) (rs6330) and brain-derived neutrotrophic factor (BDNF) (rs6265) genes predict the response to cognitive behaviour therapy (CBT). Neurotrophic genes represent plausible candidate genes: they are implicated in synaptic plasticity, response to stress, and are widely expressed in brain areas involved in mood and cognition. Allelic variation at both loci has shown associations with anxiety-related phenotypes. A sample of 374 anxiety-disordered children with white European ancestry was recruited from clinics in Reading, UK, and in Sydney, Australia. Participants received manualised CBT treatment and DNA was collected from buccal cells using cheek swabs. Treatment response was assessed at post-treatment and follow-up time points. We report first evidence that children with one or more copies of the T allele of NGF rs6330 were significantly more likely to be free of their primary anxiety diagnosis at follow-up (OR = 0.60 (0.42-0.85), P = 0.005). These effects remained even when other clinically relevant covariates were accounted for (OR = 0.62 (0.41-0.92), P = 0.019). No significant associations were observed between BDNF rs6265 and response to psychological therapy. These findings demonstrate that knowledge of genetic markers has the potential to inform clinical treatment decisions for psychotherapeutic interventions.


Home Oxygen Use and 1-Year Readmission among Infants Born Preterm with Bronchopulmonary Dysplasia Discharged from Children's Hospital Neonatal Intensive Care Units.
To determine associations between home oxygen use and 1-year readmissions for preterm infants with bronchopulmonary dysplasia (BPD) discharged from regional neonatal intensive care units. We performed a secondary analysis of the Children's Hospitals Neonatal Database, with readmission data via the Pediatric Hospital Information System and demographics using ZIP-code-linked census data. We included infants born <32 weeks of gestation with BPD, excluding those with anomalies and tracheostomies. Our primary outcome was readmission by 1 year corrected age; secondary outcomes included readmission duration, mortality, and readmission diagnosis-related group codes. A staged multivariable logistic regression was adjusted for center, clinical, and social risk factors; at each stage we included variables associated at P < .1 in bivariable analysis with home oxygen use or readmission. Home oxygen was used in 1906 of 3574 infants (53%) in 22 neonatal intensive care units. Readmission occurred in 34%. Earlier gestational age, male sex, gastrostomy tube, surgical necrotizing enterocolitis, lower median income, nonprivate insurance, and shorter hospital-to-home distance were associated with readmission. Home oxygen was not associated with odds of readmission (OR, 1.2; 95% CI, 0.98-1.56), readmission duration, or mortality. Readmissions for infants with home oxygen were more often coded as BPD (16% vs 4%); readmissions for infants on room air were more often gastrointestinal (29% vs 22%; P < .001). Clinical risk factors explained 72% of center variance in readmission. Home oxygen use is not associated with readmission for infants with BPD in regional neonatal intensive care units. Center variation in home oxygen use does not impact readmission risk. Nonrespiratory problems are important contributors to readmission risk for infants with BPD.


Accrediting osteopathic postdoctoral training institutions.
All postdoctoral training programs approved by the American Osteopathic Association are required to be part of an Osteopathic Postdoctoral Training Institution (OPTI) consortium. The author reviews recent activities related to OPTI operations, including the transfer the OPTI Annual Report to an electronic database, revisions to the OPTI Accreditation Handbook, training at the 2010 OPTI Workshop, and new requirements of the American Osteopathic Association Commission on Osteopathic College Accreditation. The author also reviews the OPTI accreditation process, cites common commendations and deficiencies for reviews completed from 2008 to 2010, and provides an overview of plans for future improvements.


A canonical promoter organization of the transcription machinery and its regulators in the Saccharomyces genome.
The predominant organizational theme by which the transcription machinery and chromatin regulators are positioned within promoter regions or throughout genes in a genome is largely unknown. We mapped the genomic location of diverse representative components of the gene regulatory machinery in Saccharomyces cerevisiae to an experimental resolution of <40 bp. Sequence-specific gene regulators, chromatin regulators, mediator, and RNA polymerase (Pol) II were found primarily near the downstream border from the "-1" nucleosome, which abuts against the approximately 140-bp nucleosome-free promoter region (NFR). General transcription factors TFIIA, -B, -D, -E, -F, -H were located near the downstream edge from the NFR. The -1 nucleosome dissociated upon Pol II recruitment, but not upon recruitment of only TBP and TFIIB. The position of many sequence-specific regulators in promoter regions correlated with the position of specific remodeling complexes, potentially reflecting functional interactions. Taken together the findings suggest that the combined action of activators and chromatin remodeling complexes remove the -1 nucleosome after the preinitiation complex (PIC) has partially assembled, but before or concomitant with Pol II recruitment. We find PIC assembly, which includes Pol II recruitment, to be a significant rate-limiting step during transcription, but that additional gene-specific rate-limiting steps associated with Pol II occur after recruitment.


Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands.
Inflammatory (Ly6C(hi) CCR2+) monocytes provide defense against infections but also contribute to autoimmune diseases and atherosclerosis. Monocytes originate from bone marrow and their entry into the bloodstream requires stimulation of CCR2 chemokine receptor by monocyte chemotactic protein-1 (MCP1). How monocyte emigration from bone marrow is triggered by remote infections remains unclear. We demonstrated that low concentrations of Toll-like receptor (TLR) ligands in the bloodstream drive CCR2-dependent emigration of monocytes from bone marrow. Bone marrow mesenchymal stem cells (MSCs) and their progeny, including CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells, rapidly expressed MCP1 in response to circulating TLR ligands or bacterial infection and induced monocyte trafficking into the bloodstream. Targeted deletion of MCP1 from MSCs impaired monocyte emigration from bone marrow. Our findings suggest that bone marrow MSCs and CAR cells respond to circulating microbial molecules and regulate bloodstream monocyte frequencies by secreting MCP1 in proximity to bone marrow vascular sinuses.


Delivery of paeonol by nanoparticles enhances its in vitro and in vivo antitumor effects.
Paeonol (Pae; 2'-hydroxy-4'-methoxyacetophenone) has attracted intense attention as a potential therapeutic agent against various cancers. However, the use of Pae is limited owing to its hydrophobicity. Recently, biodegradable polymeric nanoparticles with amphiphilic copolymers have been used as drug carriers; these have better bioavailability and are promising tumor-targeted drug delivery systems. In the current study, we prepared Pae-loaded nanoparticles (Pae-NPs) with amphiphilic block copolymers using nanoprecipitation. The physiochemical characteristics and antitumor effects of nanoparticles were evaluated in different cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed substantial inhibition of cell growth by Pae-NPs. Moreover, lower doses of Pae-NPs inhibited cell growth more efficiently than the equivalent doses of free Pae. Inhibition was characterized by significant elevation of intracellular reactive oxygen species and subsequent inhibition of Akt and regulation of apoptotic proteins, which could be partly reversed by pretreatment with the antioxidant N-acetylcysteine. In vivo results also demonstrated that Pae-NPs could exert much stronger antitumor effects than free Pae. Therefore, Pae-NPs represent a promising delivery system to overcome the low solubility of Pae and enable its use in treating cancer.


Population Variation and Genetic Control of Modular Chromatin Architecture in Humans.
Chromatin state variation at gene regulatory elements is abundant across individuals, yet we understand little about the genetic basis of this variability. Here, we profiled several histone modifications, the transcription factor (TF) PU.1, RNA polymerase II, and gene expression in lymphoblastoid cell lines from 47 whole-genome sequenced individuals. We observed that distinct cis-regulatory elements exhibit coordinated chromatin variation across individuals in the form of variable chromatin modules (VCMs) at sub-Mb scale. VCMs were associated with thousands of genes and preferentially cluster within chromosomal contact domains. We mapped strong proximal and weak, yet more ubiquitous, distal-acting chromatin quantitative trait loci (cQTL) that frequently explain this variation. cQTLs were associated with molecular activity at clusters of cis-regulatory elements and mapped preferentially within TF-bound regions. We propose that local, sequence-independent chromatin variation emerges as a result of genetic perturbations in cooperative interactions between cis-regulatory elements that are located within the same genomic domain.


Small bowel adenocarcinoma complicating Crohn's disease: case series and review of the literature.
Colonic adenocarcinoma frequently complicates inflammatory bowel disease of the colon, but small bowel adenocarcinoma (SBA) is a rare complication of Crohn's disease (CD). We present two patients with SBA in CD and review the literature with regards to CD-related SBA. A 45-year-old male with a 17-year history of ileal CD presented with obstructive symptoms but no radiographic evidence of a mass. After laparoscopic ileocolectomy and repair of incidental ileosigmoid fistula, pathology showed a T3N0 adenocarcinoma within the ileal CD. Two years after his resection he was without evidence of disease. A 59-year-old male with a 15-year history of CD presented with an acute exacerbation. Small bowel follow through demonstrated a long ileal stricture for which he underwent an ileocolic resection. Postoperative pathology confirmed a T3N1 CD-related SBA. He died from metastatic cancer 3 months later. Review of the literature identified 154 cases of SBA complicating CD with several distinguishing features from de novo SBA. Patients with SBA and CD are, as a group, younger and more likely to be male. SBA is rarely diagnosed preoperatively in these patients, and has a poor prognosis due to its advanced stage at diagnosis.


The Frequency of Huntington Disease and Huntington Disease-Like 2 in the South African Population.
Huntington disease (HD) has most recently been estimated to affect between 10.6 and 13.7 per 100,000 individuals in European populations. However, prevalence is known to differ geographically. In South Africa, the only published estimates are from a survey performed in the 1970s, an era when the disease was believed to be rare or absent in black individuals and molecular confirmation was absent. The disease phenotype in South Africa is currently attributable to mutations in both the huntington and junctophilin-3 genes, which underlie the well-known HD and the rarer HD-like 2 (HDL2) respectively. This study aimed at providing improved minimum estimates of disease frequency in South Africa, based on molecular genetic testing data. A review of all testing records for HD and HDL2 over a 20-year period was undertaken. HDL2 is virtually indistinguishable on clinical features, thus necessitating its inclusion. Based on molecular diagnostic records, minimum estimates of disease frequency are: 5.1, 2.1 and 0.25 (per 100,000 individuals) for the white, mixed ancestry and black population groups respectively. Although ascertainment remains incomplete, these minimum estimates suggest that disease frequencies are significantly higher than those previously reported in South Africa.


Intimate partner violence and its contribution to mental disorders in men and women in the post genocide Rwanda: findings from a population based study.
In low income countries, mental disorders are a neglected health problem. Mental disorders are influenced by a number of factors in people's everyday life of which intimate partner violence (IPV) commonly form an important part. The aim of this study was to investigate the prevalence of mental disorders in young men and women in Rwanda and their risk factors with main emphasis on IPV and its contribution to mental disorders, taking into account the genocide context. This population-based study included a representative sample of 917 men and women aged 20-35 years. The prevalence of mental disorders was investigated using of a diagnostic tool, the "MINI: Mini International Neuropsychiatric Interview". Risk factor patterns were analysed with bi- and multivariate logistic regression. To find the proportion of mental disorders attributed to IPV, the population attributable fraction was computed. The prevalence rates of current depression, suicide risk and PTSD were more than two times higher in women than in men while for generalized anxiety disorder, the prevalence was about the same. Physical, sexual and psychological intimate partner violence exposure was highly associated with all forms of mental disorders for women. For physical violence, after adjusting for socio-demographic factors and exposure to traumatic episodes during the Rwandan genocide, the risk of current depression for women was elevated four times. Even though few men reported partner violence exposure, physical violence in the past year was found to be a statistically significant risk factor for current depression and for generalized anxiety disorder. However, having an experience of traumatic episodes during the genocide contributed to the risk of most of mental disorders investigated for men. In Rwanda, IPV contributed considerably to mental disorders investigated. Thus, prevention of IPV should be considered as a public health priority, as its prevention would considerably reduce the prevalence of mental disorders.


Structurally coloured contact lens sensor for point-of-care ophthalmic health monitoring.
Point-of-care (POC) diagnosis is of great significance in offering precise and personalized treatment for patients with eye diseases. Contact lenses, as a kind of popular wearable device on the eye, provide a suitable platform for the integration of biosensors for the POC diagnosis of eye diseases. However, existing contact lens sensors usually involve complex electronics and circuits, the manufacturing of which is complicated and signal readout requires additional instruments. To realize the instrument-free detection of pathologically relevant signals of eye diseases, we successfully established a structurally coloured contact lens sensor with a tunable colour in this investigation, which can directly report changes in moisture and pressure that are critical signs for xerophthalmia and glaucoma diagnosis, respectively, by altering colours. Importantly, this structurally coloured contact lens sensor is made solely from a biocompatible hydrogel, without the addition of any chemical pigments, therefore exhibiting superior biosafety and wearing comfort for wearable applications. With both excellent biocompatibility and sensing capabilities, this structurally coloured contact lens sensors thus holds great promise for instrument-free ophthalmic health monitoring, which will benefit a large proportion of the population that have a high risk of eye disease.


Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families.
Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discussed.


Extinction recall of fear memories formed before stress is not affected despite higher theta activity in the amygdala.
Stress is known to exert its detrimental effects not only by enhancing fear, but also by impairing its extinction. However, in earlier studies stress exposure preceded both processes. Thus, compared to unstressed animals, stressed animals had to extinguish fear memories that were strengthened by prior exposure to stress. Here, we dissociate the two processes to examine if stress specifically impairs the acquisition and recall of fear extinction. Strikingly, when fear memories were formed before stress exposure, thereby allowing animals to initiate extinction from comparable levels of fear, recall of fear extinction was unaffected. Despite this, we observed a persistent increase in theta activity in the BLA. Theta activity in the mPFC, by contrast, was normal. Stress also disrupted mPFC-BLA theta-frequency synchrony and directional coupling. Thus, in the absence of the fear-enhancing effects of stress, the expression of fear during and after extinction reflects normal regulation of theta activity in the mPFC, not theta hyperactivity in the amygdala.


Serum Adiponectin is Associated with Adverse Outcomes of Asthma in Men but Not in Women.
Murine studies suggest a beneficial effect of systemic adiponectin on asthma. Our objective was to determine the association between serum adiponectin concentrations and asthma control/severity outcomes in men and women separately. Cross-sectional and longitudinal analyses of data from years 10, 15, and 20 examinations of the prospective coronary artery risk development in young adults study in the United States were performed. Asthma was defined by self-reported provider diagnosis at or prior to year 15 examination. Outcomes included presence of active disease, number of respiratory symptoms, and number of asthma medications; as well as longitudinal decline in absolute FEV(1). Year 15 serum adiponectin concentration was the predictor variable. In a multivariable analysis of 411 eligible subjects, after adjusting for body mass index and covariates, higher serum adiponectin concentrations were associated with more frequent active disease (including more frequent use of any asthma medication), and greater number of respiratory symptoms and asthma medications among men but not among women with asthma (p for interactions between sex and adiponectin for all analyses < 0.05). Higher serum adiponectin concentrations may be independently associated with adverse clinical outcomes of asthma in men but not in women. If biological effect is confirmed in future studies, modification of systemic adiponectin concentrations may open up newer ways to treat asthma in men.


Late diagnosis of cryptorchidism: a failure of medical screening?
A retrospective review of hospital and available community records of 47 children undergoing orchidopexy in a district hospital was undertaken to determine adequacy of screening for cryptorchidism and factors associated with late referral. Twenty eight of these boys were previously examined on 108 occasions. Diagnosis was missed on 32 occasions and the record of 38 clinical examinations did not include position of testes. In the case of 16 boys (four under school age and 12 of school age) appropriate action was not taken once the diagnosis was made. Diagnosis was reliably made in school aged children but in children under the age of 1 year cryptorchidism was frequently missed by the examining doctor. It is suggested that criteria for diagnosis and referral should be agreed in any surveillance programme. Junior doctors in hospital responsible for routine clinical examination of children during admission and clinical medical officers or general practitioners during routine clinical examination of boys should be clearly instructed to examine and record the position of the testes.


The competency of foregut mesenchyme in islet mesenchyme-to-epithelial transition during embryonic development.
Potential for curative stem-cell treatments of juvenile-onset diabetes has focussed research into pancreatic islet development. Islets were previously thought to originate solely from embryonic pancreatic epithelium, but we have demonstrated that islets can originate from mesenchyme, that is, islet mesenchyme-to-epithelial transition. The aim of this study was to establish the competence of foregut mesenchyme during mesenchymal islet development. Embryonic chick pancreatic epithelium of gestational stage Hamburger-Hamilton (HH) 22 (J Morphol. 1951;88:49-92) was combined with quail stomach mesenchyme of increasing gestation (stage HH22 [n = 6], HH26 [n = 6], HH28 [n = 4], or HH31 [n = 6]). Recombinants were cultured and analysed by immunocytochemistry for coexpression of insulin and quail-specific antigen to determine the embryonic origin of islets. Recombinants constructed using stage HH22 mesenchyme yielded 34 islets, of which 35% were mesenchymal. However, when recombinants were constructed using stage HH26 mesenchyme, 24% of 25 islets were mesenchymal. When using mesenchyme, 13% of 15 islets were mesenchymal. All islets (n = 35) in recombinants constructed using stage HH31 mesenchyme were epithelial derived. Islet mesenchyme-to-epithelial transition diminished significantly with increasing mesenchymal gestational stage (P = .002). These data show foregut mesenchyme is competent to form islets between stages HH22 and HH28. Developmental competence of foregut mesenchyme in islet mesenchyme-to-epithelial transition diminishes as gestation increases. This may have important implications for identifying stem cells to treat juvenile-onset diabetes.


Paneth cells: leukocyte-like mediators of innate immunity in the intestine.
Paneth cells are secretory intestinal epithelial cells located at the base of the crypts of Lieberkühn in the small intestine. They display prominent cytoplasmic granules, containing antibacterial proteins such as lysozyme, secretory phospholipase A2 type IIA, and alpha-defensins, which are released into the intestinal lumen in response to a range of stimuli. In this, they resemble circulating leukocytes, which also elaborate and secrete lysozyme and alpha-defensins as part of an antibacterial defense function, and the resemblance is sustained at other levels. The cells also strongly and specifically express the NOD2 gene product, one of an emerging family of critical, intracellular mediators of innate immune responses, which is also highly expressed in peripheral blood mononuclear cells, and they express RNA for tumor necrosis factor alpha, a major myelomonocytic cell-derived cytokine, which has a crucial role in the pathogenesis of diseases such as rheumatoid arthritis and Crohn's disease (CD). Thus, these cells, which are derived from the pluripotent intestinal epithelial stem-cell lineage, are sessile, resident host-defense cells, which may share with leukocytes the beneficial function of secreting antimicrobial peptides, as well as the potentially harmful capacity for promoting inflammation and tissue damage. Paneth cells are most abundant in the distal small intestine, which is the region most frequently affected by CD, and there is great interest in the potential role of these cells in this condition. This brief review summarizes current knowledge and speculates on how the study of these fascinating cells might be advanced.


Optical shock waves in silica aerogel.
Silica aerogels are materials well suited for high power nonlinear optical applications. In such regime, the non-trivial thermal properties may give rise to the generation of optical shock waves, which are also affected by the structural disorder due to the porous solid-state gel. Here we report on an experimental investigation in terms of beam waist and input power, and identify various regimes of the generation of wave-breaking phenomena in silica aerogels.


Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016.
Autism spectrum disorder (ASD). 2016. The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (39% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively) [corrected]. Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months). The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.


Early immune suppression leads to uncontrolled mite proliferation and potent host inflammatory responses in a porcine model of crusted versus ordinary scabies.
Scabies is a neglected tropical disease of global significance. Our understanding of host-parasite interactions has been limited, particularly in crusted scabies (CS), a severe clinical manifestation involving hyper-infestation of Sarcoptes scabiei mites. Susceptibility to CS may be associated with immunosuppressive conditions but CS has also been seen in cases with no identifiable risk factor or immune deficit. Due to ethical and logistical difficulties with undertaking research on clinical patients with CS, we adopted a porcine model which parallels human clinical manifestations. Transcriptomic analysis using microarrays was used to explore scabies pathogenesis, and to identify early events differentiating pigs with ordinary (OS) and crusted scabies. Pigs with OS (n = 4), CS (n = 4) and non-infested controls (n = 4) were compared at pre-infestation, weeks 1, 2, 4 and 8 post-infestation. In CS relative to OS, there were numerous differentially expressed genes including pro-inflammatory cytokines (IL17A, IL8, IL19, IL20 and OSM) and chemokines involved in immune cell activation and recruitment (CCL20, CCL27 and CXCL6). The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS. This is the first comprehensive study describing transcriptional changes associated with the development of CS and significantly, the distinction between OS and CS. This provides a basis for clinical follow-up studies, potentially identifying new control strategies for this severely debilitating disease.


Urinary functional outcome following radical cystoprostatectomy and ileal neobladder reconstruction in male patients.
Orthotopic neobladder reconstruction is the preferred method of urinary diversion after radical cystoprostatectomy. We evaluated urinary functional outcomes in male patients after orthotopic neobladder using a patient questionnaire. Between 2002 and 2009 patients with bladder cancer were enrolled in a clinical trial, randomly assigned to undergo T pouch or Studer pouch diversion after radical cystoprostatectomy. Male patients were mailed a questionnaire 12 or more months after surgery including items on urinary function, intermittent catheterization, number/size/wetness of pads and mucus leakage. The questionnaire response rate was 68%. Mean followup was 4.5 years (range 1 to 8). Only 22.3% of patients did not use pads. In the daytime 47% of patients used at least 1 pad, 32.2% used small/mini pads and 22.6% used diapers. At night 72% used pads, 14.7% used small/mini pads and 38.9% used diapers. During the day and night 47% said their pads were dry/barely wet. Overall 62.5% of patients reported mucus leakage. Only 9.5% of patients performed clean intermittent self-catheterization, of whom 70.6% started clean intermittent self-catheterization within the first year after surgery. Increasing age and diabetes mellitus were predictors of urinary function (p = 0.005 and 0.03, respectively) but did not affect pad use. Ileal orthotopic neobladder offers good functional results but most patients wear at least 1 pad and many require diapers at night. Increasing age and diabetes mellitus predict worse urinary function but are not associated with pad use. Emptying failure is uncommon and occurs early in the postoperative period. Pad size/wetness and mucus leakage should be considered when evaluating urinary incontinence.


An I2-mediated aerobic oxidative annulation of amidines with tertiary amines via C-H amination/C-N cleavage for the synthesis of 2,4-disubstituted 1,3,5-triazines.
An iodine-mediated formal oxidative cycloaddition of amidines with tertiary amines was first demonstrated in air. Both symmetrical and unsymmetrical 2,4-disubstituted 1,3,5-triazines were obtained in up to 85% yields. It is noted that a tertiary amine was employed as a one carbon synthon of 1,3,5-triazines and two C-N bonds were formed in one pot. Control experiments revealed that the reaction underwent a radical pathway promoted by I+. The method is transition-metal-free, peroxide-free, and operationally simple to implement with a wide scope of substrates.


The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study.
The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance. The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method. The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance. The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.


Relative growth of the skull and postcranium in giant transgenic mice.
Cross-sectional allometric growth patterns of the cranial and postcranial skeleton were compared between giant transgenic (MT-rGH) mice and their normal littermate controls. Body weights, external body dimensions, and a series of cranial and postcranial linear dimensions of the skeleton were determined for samples of known age. Comparative bivariate and multivariate allometric analyses were completed in order to determine whether (1) the larger transgenic mice differed significantly from the normal controls in aspects of body and skeletal proportions, and (2) any such proportion differences resulted from general allometric effects of overall weight or skeletal size increase. Results demonstrate that the transgenic mice do exhibit significantly different body and skeletal proportions than normal control adults. Allometric comparisons of the skeletal dimensions relative to body weight reveal similar coefficients of growth allometry but several differences in gamma-intercept values in the transgenic vs. control groups. The comparisons among the skeletal dimensions of the skull and postcranium generally reveal the sharing and differential extension of common growth allometries in the two groups. Thus, the elevated levels of growth hormone (GH) and insulin-like growth factor I (IGF-I) in the transgenic mice appear to result in increased overall growth for the various skeletal elements, but in the relative proportions determined by intrinsic growth controls within that system.


Freshwater submersion injuries in children: a retrospective review of seventy-five hospitalized patients.
To determine whether or not selected victims of submersion accidents can be safely managed as outpatients. Retrospective chart review. Children's Medical Center of Dallas. One hundred forty-eight charts reviewed, comprising all hospital admissions after submersion accidents from April 1987 to April 1994. Of the 148 patient charts that were reviewed, 73 patients were excluded from the study for the following criteria: endotracheal intubation before initial medical evaluation; transfer form an inpatient unit of another medical facility; history of preexisting neurologic, neurodevelopmental, and/or pulmonary disease. Of the 75 evaluable patients, 3 were directly admitted to the inpatient service with no documented initial medical evaluation reported in the medical record. Of the remaining 72 patients, 62 (86%) were symptomatic at the time of the initial medical evaluation in the emergency department; 10 patients (14%) were asymptomatic. Seventy percent of the initially asymptomatic patients and 57% of patients who were symptomatic at the time of initial medical evaluation were asymptomatic by 8 hours after the submersion event. By 18 hours postsubmersion, all patients who were initially asymptomatic and 72% of initially symptomatic patients were normal. Thirty-five percent and 80% of patients who had abnormal initial physical examinations and abnormal chest x-rays had a normal physical examination by 8 hours and 18 hours, respectively, and all remained normal. Routine hospital admission of all children who have had immersion accidents is unnecessary.


Multivitamins and minerals modulate whole-body energy metabolism and cerebral blood-flow during cognitive task performance: a double-blind, randomised, placebo-controlled trial.
The brain is by far the most metabolically active organ in the body, with overall energy expenditure and local blood-supply closely related to neural activity. Both energy metabolism and cerebral vaso-dilation are dependent on adequate micronutrient status. This study investigated whether supplementation with ascending doses of multi-vitamin/minerals could modulate the metabolic and cerebral blood-flow consequences of performing cognitive tasks that varied in difficulty. In this randomised, double-blind, placebo-controlled, parallel-groups study 97 healthy females (25-49 y), who were not selected on the basis of any nutritional parameters, received either placebo or one of two doses of multivitamins/minerals. Cerebral blood-flow (CBF) parameters in the frontal cortex, and total energy expenditure (TotalEnergy), carbohydrate and fat oxidation (CarbOxi/FatOxi), were measured during 5 tasks of graded cognitive difficulty and a control task (5 min per task) using Near-infrared spectroscopy (NIRS) and Indirect calorimetry of exhaled pulmonary gas (ICa) respectively. Assessments took place 60 min after the first dose and following eight weeks supplementation. During task performance supplementation with the first dose of micronutrients led to a dose-dependent increase in TotalEnergy and FatOxi throughout the post-dose assessment period following the higher dose, and increases in the total concentration of haemoglobin, a proxy measure for CBF, during task performance following the lower dose of vitamins/minerals (also containing coenzyme-Q10). Chronic supplementation over 8 weeks led to a dose-dependent increase in TotalEnergy during the task period. There were no interpretable effects on mood or cognitive performance. These results show that acute supplementation with micronutrients in healthy adults can modulate metabolic parameters and cerebral blood flow during cognitive task performance, and that the metabolic consequences are sustained during chronic supplementation. These findings suggest that both brain function and metabolism are amenable to micronutrient supplementation, even in adults who are assumed to have nutritional status typical of the population. ClinicalTrials.gov - NCT02381964.


A review of the Liverpool elbow prosthesis from 1974 to 1982.
Eighty elbows in 65 patients with an average age of 57 years have had two-part non-constrained Liverpool elbow arthroplasties performed since 1974. Fifty-five had rheumatoid arthritis, eight osteoarthritis or ankylosis secondary to injury, one osteochondritis dissecans and one pyknodysostosis. The average preoperative range of movement was 42 degrees to 112 degrees with 47 degrees of pronation and 42 degrees of supination. There was significant gain in the arc of movements at follow-up: 32 degrees in the extension-flexion range (average range 32 degrees to 134 degrees of flexion) and 42 degrees in forearm rotation (average pronation 69 degrees and supination 62 degrees). Before operation severe pain was the predominating symptom in 43 elbows (53.8%) but after replacement there was only moderate pain in five elbows (6.2%). The results were excellent in 42 (52.5%), good in 15 (18.7%), fair in 9 (11.3%) and unsatisfactory or poor in 14 (17.5%). Eight elbows required revision of the arthroplasty: three were post-traumatic, disorganised or osteoarthritic joints, three rheumatoid and both elbows in the patient with pyknodysostosis. Loosening of the prosthesis (particularly the humeral component) was the common factor necessitating revision. Of six rheumatoid elbows needing removal of the implant, four had deep infection, one had a dislodged humeral component as a result of injury and in one a divided olecranon had developed non-union. Rheumatoid elbows benefited more than post-traumatic arthritic elbows from the operation. (ABSTRACT TRUNCATED AT 250 WORDS)


Dynamic environments do not appear to constrain spider web building behaviour.
Many laboratory experiments demonstrate how orb-web spiders change the architecture of their webs in response to prey, surroundings and wind loading. The overall shape of the web and a range of other web parameters are determined by frame and anchor threads. In the wild, unlike the lab, the anchor threads are attached to branches and leaves that are not stationary but move, which affects the thread tension field. Here we experimentally test the effect of a moving support structure on the construction behaviour and web-parameters of the garden cross spider Araneus diadematus. We found no significant differences in building behaviour between rigid and moving anchors in total time spent and total distance covered nor in the percentage of the total time spent and distance covered to build the three major web components: radials, auxiliary and capture spirals. Moreover, measured key parameters of web-geometry were equally unaffected. These results call for re-evaluation of common understanding of spider webs as thread tensions are often considered to be a major factor guiding the spider during construction and web-operation.


Cardiac rehabilitation services in England and Wales: a national survey.
We sent a short postal questionnaire to 244 centres in England and Wales that admitted patients with cardiac conditions. In total, 199 (81%) of the centres claimed to provide a cardiac rehabilitation service. Of these, 25 were randomly selected as a representative sample and visited in order to obtain detailed information concerning the provision of services. Most (18 (72%)) of the centres had commenced their rehabilitation programme within the previous 5 years, usually at the instigation of interested staff. Patient entry to cardiac rehabilitation programmes was restricted; women (who represented only 15% of attenders), elderly people (excluded in 10 (40%) centres), and those with more complex problems, such as angina or heart failure, were under-represented. The central components of all programmes were education and exercise training but there was a wide range in the quantity and quality of service provision. Most (22 (88%)) programmes were hospital out-patient based, one (4%) was hospital in-patient based, one (4%) was community-based and one (4%) was home-based. The staffing and funding of programmes was variable, with 7 (28%) having no identified funding. There are wide variations in the resources currently available for the rehabilitation of patients with coronary heart disease. There is a need for clearer direction of these services, in particular to determine minimum service provision. Guidelines are necessary to give a framework for this relatively new and rapidly expanding service.


Prediction of retail product weight and percentage using ultrasound and carcass measurements in beef cattle.
Data from 534 steers representing six sire breed groups were used to develop live animal ultrasound prediction equations for weight and percentage of retail product. Steers were ultrasonically measured for 12th-rib fat thickness (UFAT), rump fat thickness (URPFAT), longissimus muscle area (ULMA), and body wall thickness (UBDWALL) within 5 d before slaughter. Carcass measurements included in USDA yield grade (YG) and quality grade calculations were obtained. Carcasses were fabricated into boneless, totally trimmed retail products. Regression equations to predict weight and percentage of retail product were developed using either live animal or carcass traits as independent variables. Most of the variation in weight of retail product was accounted for by live weight (FWT) and carcass weight with R2 values of 0.66 and 0.69, respectively. Fat measurements accounted for the largest portion of the variation in percentage of retail product when used as single predictors (R2 = 0.54, 0.44, 0.23, and 0.54 for UFAT, URPFAT, UBDWALL, and carcass fat, respectively). Final models (P < 0.10) using live animal variables included FWT, UFAT, ULMA, and URPFAT for retail product weight (R2 = 0.84) and UFAT, URPFAT, ULMA, UBDWALL, and FWT for retail product percentage (R2 = 0.61). Comparatively, equations using YG variables resulted in R2 values of 0.86 and 0.65 for weight and percentage of retail product, respectively. Results indicate that live animal equations using ultrasound measurements are similar in accuracy to carcass measurements for predicting beef carcass composition, and alternative ultrasound measurements of rump fat and body wall thickness enhance the predictive capability of live animal-based equations for retail yield.


Anti-angiogenic potential of Gleditsia sinensis fruit extract.
Blood supply plays a crucial role in solid tumour development and leukaemogenesis. It has been suggested that blocking of angiogenesis could be possible in cancer therapy. We have demonstrated the antiproliferative activity of Gleditsia sinensis fruit extract (GSE) on various human solid tumour cancer cell lines as well as leukaemia cell lines and primary cultured leukaemia cells obtained from leukaemia patients. However, the antiangiogenic potential of GSE has not been demonstrated. Here we demonstrated that GSE could reduce vascular endothelial growth factor (VEGF) mRNA expression in dose- and time course-dependently in MDA-MB231 breast cancer and HepG2 hepatoblastoma cell lines as measured by reverse transcriptase polymerase chain reaction. Enzyme-linked immunosorbent assay further showed that GSE could reduce the VEGF secretion from various cancer cell lines including MDA-MB231, HepG2, HL-60 (acute promyelocytic leukaemia) and eleven primary cultured leukaemia cells obtained from acute myelogenous leukaemia patients. In vivo chick chorioallantoic membrane assay illustrated that GSE could reduce the angiogenic activity of basic fibroblast growth factor. Taken together, the information suggested that GSE could be potentially used as an angiogenic inhibitor in both solid tumour and leukaemia therapy.


The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome.
Gastric acidity is likely a key factor shaping the diversity and composition of microbial communities found in the vertebrate gut. We conducted a systematic review to test the hypothesis that a key role of the vertebrate stomach is to maintain the gut microbial community by filtering out novel microbial taxa before they pass into the intestines. We propose that species feeding either on carrion or on organisms that are close phylogenetic relatives should require the most restrictive filter (measured as high stomach acidity) as protection from foreign microbes. Conversely, species feeding on a lower trophic level or on food that is distantly related to them (e.g. herbivores) should require the least restrictive filter, as the risk of pathogen exposure is lower. Comparisons of stomach acidity across trophic groups in mammal and bird taxa show that scavengers and carnivores have significantly higher stomach acidities compared to herbivores or carnivores feeding on phylogenetically distant prey such as insects or fish. In addition, we find when stomach acidity varies within species either naturally (with age) or in treatments such as bariatric surgery, the effects on gut bacterial pathogens and communities are in line with our hypothesis that the stomach acts as an ecological filter. Together these results highlight the importance of including measurements of gastric pH when investigating gut microbial dynamics within and across species.


Health related quality of life in adolescents with chronic fatigue syndrome: a cross-sectional study.
To study health related quality of life (HRQOL) and depressive symptoms in adolescents with chronic fatigue syndrome (CFS) and to investigate in which domains their HRQOL and depressive symptoms differ from those of healthy adolescents. Several symptoms such as disabling fatigue, pain and depressive symptoms affect different life domains of adolescents with CFS. Compared to adolescents with other chronic diseases, young people with CFS are reported to be severely impaired, both physiologically and mentally. Despite this, few have investigated the HRQOL in this group. This is a cross-sectional study on HRQOL including 120 adolescents with CFS and 39 healthy controls (HC), between 12 and 18 years. The Pediatric Quality of Life Inventory™, 4.0 (PedsQL) was used to assess HRQOL. The Mood and Feelings Questionnaire assessed depressive symptoms. Data were collected between March 2010 and October 2012 as part of the NorCAPITAL project (Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial). Linear and logistic regression models were used in analysis, and all tests were two-sided. Adolescents with CFS reported significantly lower overall HRQOL compared to HCs. When controlling for gender differences, CFS patients scored 44 points lower overall HRQOL on a scale from 0-100 compared to HCs. The domains with the largest differences were interference with physical health (B = -59, 95 % CI -54 to -65) and school functioning (B = -52, 95 % CI -45 to -58). Both depressive symptoms and being a patient were independently associated with lower levels of HRQOL CONCLUSION: The difference in HRQOL between CFS patients and healthy adolescents was even larger than we expected. The large sample of adolescents with CFS in our study confirms previous findings from smaller studies, and emphasizes that CFS is a seriously disabling condition that has a strong impact on their HRQOL. Even though depressive symptoms were found in the group of patients, they could not statistically explain the poor HRQOL.


Visceral adiposity, insulin resistance and cancer risk.
There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.


Intermediate and long-term outcomes of total ankle arthroplasty and ankle arthrodesis. A systematic review of the literature.
The efficacy of total ankle replacement compared with that of ankle fusion continues to be one of the most debated topics in foot and ankle surgery. The purpose of this study was to determine whether there are sufficient objective cumulative data in the literature to compare the two procedures. A systematic review of the literature addressing the intermediate and long-term outcomes of interest in total ankle arthroplasty and ankle arthrodesis was performed. A comprehensive search of MEDLINE for all relevant articles published in English from January 1, 1990, to March 2005 was conducted. Additionally, relevant abstracts from the 2003 and 2004 annual proceedings of major orthopaedic meetings were eligible. Two reviewers evaluated each study to determine whether it was eligible for inclusion and collected the data of interest. Meta-analytic pooling of group results across studies was performed for the two procedures. The analysis of the outcomes focused on second-generation ankle implants. The systematic review identified forty-nine primary studies, ten of which evaluated total ankle arthroplasty in a total of 852 patients and thirty-nine of which evaluated ankle arthrodesis in a total of 1262 patients. The mean AOFAS (American Orthopaedic Foot and Ankle Society) Ankle-Hindfoot Scale score was 78.2 points (95% confidence interval, 71.9 to 84.5) for the patients treated with total ankle arthroplasty and 75.6 points (95% confidence interval, 71.6 to 79.6) for those treated with arthrodesis. Meta-analytic mean results showed 38% of the patients treated with total ankle arthroplasty had an excellent result, 30.5% had a good result, 5.5% had a fair result, and 24% had a poor result. In the arthrodesis group, the corresponding values were 31%, 37%, 13%, and 13%. The five-year implant survival rate was 78% (95% confidence interval, 69.0% to 87.6%) and the ten-year survival rate was 77% (95% confidence interval, 63.3% to 90.8%). The revision rate following total ankle arthroplasty was 7% (95% confidence interval, 3.5% to 10.9%) with the primary reason for the revisions being loosening and/or subsidence (28%). The revision rate following ankle arthrodesis was 9% (95% confidence interval, 5.5% to 11.6%), with the main reason for the revisions being nonunion (65%). One percent of the patients who had undergone total ankle arthroplasty required a below-the-knee amputation compared with 5% in the ankle arthrodesis group. On the basis of these findings, the intermediate outcome of total ankle arthroplasty appears to be similar to that of ankle arthrodesis; however, data were sparse. Comparative studies are needed to strengthen this conclusion.


Cost-effectiveness of computed tomographic colonography screening for colorectal cancer in the medicare population.
The Centers for Medicare and Medicaid Services (CMS) considered whether to reimburse computed tomographic colonography (CTC) for colorectal cancer screening of Medicare enrollees. To help inform its decision, we evaluated the reimbursement rate at which CTC screening could be cost-effective compared with the colorectal cancer screening tests that are currently reimbursed by CMS and are included in most colorectal cancer screening guidelines, namely annual fecal occult blood test (FOBT), flexible sigmoidoscopy every 5 years, flexible sigmoidoscopy every 5 years in conjunction with annual FOBT, and colonoscopy every 10 years. We used three independently developed microsimulation models to assess the health outcomes and costs associated with CTC screening and with currently reimbursed colorectal cancer screening tests among the average-risk Medicare population. We assumed that CTC was performed every 5 years (using test characteristics from either a Department of Defense CTC study or the National CTC Trial) and that individuals with findings of 6 mm or larger were referred to colonoscopy. We computed incremental cost-effectiveness ratios for the currently reimbursed screening tests and calculated the maximum cost per scan (ie, the threshold cost) for the CTC strategy to lie on the efficient frontier. Sensitivity analyses were performed on key parameters and assumptions. Assuming perfect adherence with all tests, the undiscounted number life-years gained from CTC screening ranged from 143 to 178 per 1000 65-year-olds, which was slightly less than the number of life-years gained from 10-yearly colonoscopy (152-185 per 1000 65-year-olds) and comparable to that from 5-yearly sigmoidoscopy with annual FOBT (149-177 per 1000 65-year-olds). If CTC screening was reimbursed at $488 per scan (slightly less than the reimbursement for a colonoscopy without polypectomy), it would be the most costly strategy. CTC screening could be cost-effective at $108-$205 per scan, depending on the microsimulation model used. Sensitivity analyses showed that if relative adherence to CTC screening was 25% higher than adherence to other tests, it could be cost-effective if reimbursed at $488 per scan. CTC could be a cost-effective option for colorectal cancer screening among Medicare enrollees if the reimbursement rate per scan is substantially less than that for colonoscopy or if a large proportion of otherwise unscreened persons were to undergo screening by CTC.


Interventions to promote the wearing of hearing protection.
This is an update of a Cochrane Review first published in The Cochrane Library in Issue 2, 2006 and previously updated in 2009.Noise-induced hearing loss can be prevented by eliminating or lowering noise exposure levels. Where the source of the noise cannot be eliminated, workers have to rely on hearing protection equipment. Several trials have been conducted to study the effectiveness of interventions to influence the wearing of hearing protection. To evaluate the effectiveness of interventions to enhance the wearing of hearing protection among persons regularly exposed to high noise levels. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 8 April 2011. We included studies if they had a randomised design, if they were among noise exposed (> 80 dB(A)) persons, if they included an intervention to promote the wearing of hearing protection (compared to another intervention or no intervention), and if the outcome measured was the amount of use of hearing protection or a proxy measure thereof. Two authors selected relevant trials, assessed risk of bias and extracted data. Seven studies, involving 4670 participants, were included.A computer-based intervention lasting 30 minutes, tailored to the risk of an individual worker, was not found to be more effective than a video providing general information among workers, around 80% of whom already used hearing protection.A four-year school-based hearing loss prevention programme found that the intervention group was twice as likely to wear some kind of hearing protection as the control group that received a baseline hearing test and two additional tests at years two and three.We conducted two meta-analyses for the comparisons 'tailored strategy (the use of communication or other types of interventions that are specific to an individual or a group and aim to change behaviour) versus non-tailored strategy' and 'tailored strategy versus a commercial video on the use of hearing protection' to look at mean percentage use of hearing protective devices (HPDs), that showed improvement in the mean use of HPDs for the tailored group. A meta-analysis of the comparison 'mixed interventions' (classroom instruction, distribution of HPDs, mailings, noise level assessments and audiometric testing) versus control (audiometric testing alone) also showed improvement in self reported use of HPDs when shooting firearms.Tailored education showed an improvement in HPD use of 8.3% versus targeted education (6.1%). The evidence found in this review shows that some interventions improve the mean use of hearing protection devices compared to non-intervention. Future trials should have standard outcomes and interventions to allow the combining of results in meta-analysis.